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| |  MPS-I Patients Taking Alpha-L-Iduronidase Show Marked Improvement, Study Shows CAMBRIDGE, MA and NOVATO, CA -- Oct. 30, 1998 -- Patients with the fatal genetic disorder mucopolysaccharidosis (MPS-I) showed substantial improvement when treated with Genzyme General’s enzyme alpha-L-iduronidase in a recently concluded pivotal clinical trial. The trial results were presented today at the American Society of Human Genetics annual meeting in Denver. MPS-I results from a genetic deficiency in the production of alpha-L- iduronidase, a key enzyme required for the progressive breakdown of complex carbohydrates found in all cells of the body. Data from the trial demonstrated that alpha-L-iduronidase replacement therapy reduced clinical measurements of the disease and improved patients' ability to perform normal functions of daily life. "The trial results are very encouraging," said Emil D. Kakkis, M.D., Ph.D., the study's principal investigator, who presented the findings. "This clinical trial culminates 30 years of research and marks the first time enzyme replacement therapy has been used effectively with MPS-I patients." The clinical trial, which was initiated in December 1997 and conducted at the Harbor-UCLA Research and Education Institute in Torrance, CA., in collaboration with four other leading medical centres, enrolled 10 patients in a 26-week treatment protocol. MPS-I strikes children, with initial diagnosis typically at two or three years of age. The ages of those enrolled in the trial ranged from five to 22 years. Patients were evaluated before the trial began to establish a clinical baseline. They were then given a weekly intravenous infusion of 125,000 units (0.5mg) of alpha-L-iduronidase per kilogram of body weight. Patients were subsequently examined after weeks six, 12 and 26. Both quantitative data and clinical/patient self-assessment data were collected and analysed. Quantitative MRI studies demonstrated that treatment with a-L-iduronidase was associated with a rapid 20 percent or more reduction in liver size after six to 12 weekly doses in nearly all patients and that liver size returned to normal in the majority of patients by 26 weeks. Patients also showed a decrease in the excretion of urinary glycosaminoglycans, indicating the success of alpha-L-iduronidase in breaking down these complex carbohydrate materials, which otherwise will accumulate in patients with MPS-I. Urinary glycosaminoglycan levels typically dropped by the third or fourth dose of the enzyme and all patients achieved a 60 percent or better reduction within 12 weeks. In addition, patients reported improvements in physical abilities and quality of life. Joint pain was reduced and mobility improved, allowing patients to do more activities that had been difficult before, such as walk, run, swim, hang from monkey bars, or swing a bat. Patients also had substantial improvements in endurance and decreased fatigue. Difficulties in breathing were much improved and contributed to the improved endurance. For several patients, limited half days at school were extended to full days. The severe headaches with occasional vomiting that plagued some patients up to several times a week prior to treatment, were resolved after several weeks of therapy. Hearing and vision improved in certain patients. Adverse events such as hives were noted in a minority of patients but were manageable and did not significantly affect the patients' health. All patients who were enrolled in the trial continue to receive therapy and will be evaluated at 12 and 18 months following the initiation of treatment. The FDA has designated alpha-L-iduronidase a fast-track product. MPS-I encompasses three syndromes -- Hurler, Hurler-Scheie and Scheie syndromes -- that define ranges in a spectrum of severity. All types of MPS-I are caused by a deficiency in an active enzyme, alpha-L-iduronidase, which results in a build-up of carbohydrate materials called glycosaminoglycans in all tissues of the body. This build-up of stored material leads to cell, tissue and organ dysfunction. The debilitating effects of MPS-I lead to early death -- often before the age of 10 . Symptoms can include enlargement of the liver and spleen, joint pain and immobility, skeletal deformity, vision impairment, stunted growth, hearing loss, obstruction of airways, severe headaches and cardiomyopathy. Approximately 2,000-3,000 patients in the developed world have been diagnosed with MPS-I. As with other lysosomal storage diseases, there are believed to be additional undiagnosed patients. There is currently no known effective treatment for MPS-I.
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